Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus

Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus
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博纳病病毒大鼠鼻内感染后病毒传播动力学及脑内几种细胞因子mRNA水平的变化

DOI:
10.1128/jvi.66.2.992-998.1992
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发表时间:
1992
影响因子:
5.4
通讯作者:
B. Dietzschold
B. Dietzschold
中科院分区:
医学2区
文献类型:
--
作者:
V. Shankar;M. Kao;A. Hamir;Hai Sheng;H. Koprowski;B. Dietzschold

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本研究应用逆转录-聚合酶链反应技术对博尔纳病病毒(BDV)引起的脑炎进行了研究。在感染后6天(p.i.),在鼻内感染大鼠的嗅球中首次检测到BDV特异性RNA。注射后14天,在所有脑区域中发现高水平的BDV RNA,并且在感染后26天,BDV特异性RNA也存在于眼睛、鼻粘膜和面部皮肤中。在疾病的慢性阶段,在许多外周器官中鉴定出BDV RNA,但在血液中未鉴定出。对脑组织细胞因子mRNA存在的分析显示,白细胞介素-6(IL-6)、肿瘤坏死因子α和IL-1 α的mRNA水平在感染后14天和26天急剧增加。这些细胞因子mRNA在炎症反应的高峰期达到最高水平,并在疾病的慢性期急剧下降。虽然IL-2 mRNA也在正常脑中发现,但在感染后14天,在感染BDV的脑中IL-2 mRNA显著增加。在感染后14天检测到γ干扰素(IFN-γ)mRNA的表达,这在正常大鼠脑中未观察到。并在感染后38天达到最高水平。IL-2和IFN-γ mRNA表达与CD 4和CD 8 mRNA表达相关,表明CD 4+和CD 8 + T淋巴细胞在BDV感染的早期阶段被诱导。由于IFN-γ和CD 8 mRNA水平在博尔纳病的慢性期仍然高度升高,因此CD 8 + T淋巴细胞可能在感染的慢性期起到减少炎症和改善神经体征的作用。
We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). RNA specific for BDV was first detected in the olfactory bulb of intranasally infected rats at 6 days postinfection (p.i.). At 14 days p.i., high levels of BDV RNA were found in all brain regions, and at 26 days p.i., BDV-specific RNA was also present in the eye, nasal mucosa, and facial skin. In the chronic phase of the disease, BDV RNA was identified in many peripheral organs but not in blood. Analysis of brain tissue for the presence of cytokine mRNAs revealed that the mRNA levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1 alpha had increased sharply at 14 and 26 days p.i. These cytokine mRNAs reached maximum levels at the peak of inflammatory reactions and decreased drastically in the chronic phase of the disease. Although IL-2 mRNA was also found in normal brain, it was markedly increased in BDV-infected brain at 14 days p.i. Expression of gamma interferon (IFN-gamma) mRNA, which was not observed in normal rat brain, was detected at 14 days p.i. and reached a maximum level at 38 days p.i. IL-2 and IFN-gamma mRNA expression correlated with expression of CD4 and CD8 mRNAs, indicating that both CD4+ and CD8+ T lymphocytes are induced in the early stages of BDV infection. Since IFN-gamma and CD8 mRNA levels were still highly elevated in the chronic phase of Borna disease, it is likely that CD8+ T lymphocytes act to reduce inflammation and to ameliorate neurological signs during the chronic phase of infection.
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